1. Field of the Invention
This invention concerns a basement-membrane protein useful in adhering keratinocytes to the dermis. More specifically, this invention concerns a method of using this protein to enhance the success of skin transplants.
2. General Background of the Invention
The use of cultured epidermal grafts (keratinocyte grafts) to treat patients with life-threatening burns was first reported by O'Conner et al., The Lancet 1:75-78 (1981). Small skin biopsy specimens from burn patients were cultured in vitro, and the cultured autografts were placed on full thickness wounds on the arms of burn patients. The cultured keratinocytes successfully grew to cover the wounds in six weeks.
Subsequent attempts have been made to improve this method by modifying it to grow keratinocytes in serum-free medium. Others have suggested using composite cadaver skin allografts resurfaced with autologous cultured keratinocytes. Attempts have also been made to use different backing materials for the cultured cells or to vary the keratinocyte culture methodology. The results of cultured keratinocyte transplants, however, have often been disappointing.
One of the most useful applications for keratinocyte grafts has been in patients with burns damaging more than half of the body surface. Such patients have insufficient donor sites to provide enough split skin thickness grafts to resurface the area of the burn after surgical excision. Unfortunately, the results of keratinocyte autografting in these circumstances have been variable and disappointing.
Cultured epidermal grafts have been found to be significantly more fragile than normal skin and more prone to blistering. Woodley et al., JAMA 259:2566-2571 (1988). Some researchers have suggested that an abnormality in one or more connective tissue components within the autografts might explain the altered epidermal-dermal adherence observed clinically. The identity of that component, however, has remained obscure.
It is an object of this invention to identify and provide a therapeutically useful form of a connective tissue component that provides epidermal-dermal adherence.
It is another object of this invention to use such a therapeutically useful substance to enhance the adhesion of transplanted cultured keratinocytes to an underlying substrate, such as a mammalian or human dermis.
These and other objects of the invention will be understood more clearly by reference to the following detailed description.